Use of soluble African horse sickness viral protein 7 as an antigen delivery and presentation system

We have investigated the use of soluble chimeric trimers of the major capsid protein VP7 of African horse sickness virus (AHSV) as a vaccine delivery system by targeting some of the natural hydrophilic loops on the VP7 top domain for the insertion of foreign peptides. Key to this trimer display strategy is the solubility of AHSV VP7 and how the solubility of this hydrophobic protein can be manipulated by inserting peptides into the top domain. To investigate, we generated different cloning vectors by inserting multiple cloning sites at three different positions in the VP7 gene. These modifications inserted six amino acids at the cloning sites and in some cases this converted VP7 to a largely soluble protein without affecting the ability of the modified proteins to form trimers. The vectors were used to generate a number of soluble VP7 fusion proteins including a fusion with a 36 amino acid insert that overlaps important immunological domains on protein VP1 of foot and mouth disease virus (FMDV) as well as a 110 amino acid peptide derived from AHSV VP2. Soluble trimers of these fusion proteins were able to elicit a good insert-specific immune response in guinea pigs. l-Arginine was found to reverse protein aggregation and was employed as an effective strategy to isolate relatively pure soluble chimeric VP7 trimers. Another factor that increased VP7 solubility in both wild-type VP7 and one of the VP7 vector proteins was the substitution of the leucine residue in position 345 of the VP7 Cterminus with a hydrophilic arginine residue.The work was largely supported by BioPad Bric grant BP050 with additional support from the National Research Foundation.www.elsevier.com/locate/virusre

A study of autopsy procedures in Ghana: Implications for the use of autopsy data in epidemiological analyses

Fobil JN, Kumoji R, Armah HB, et al. A study of autopsy procedures in Ghana: Implications for the use of autopsy data in epidemiological analyses. Journal of Public Health in Africa. 2011;2(1):e7.The study of cause of death certification remains a largely neglected field in many developing countries, including Ghana. Yet, mortality information is crucial for establishing mortality patterns over time and for estimating mortality attributed to specific causes. In Ghana, in deaths occurring in homes and those occurring within 48 hours after admission into health facilities, autopsies remain the appropriate option for determining the cause of death. Although these organ-based autopsies may generate convincing results and are considered the ‘gold standard’ tools for ascertainments of causes of death, procedural and practical constraints could limit the extent to which autopsy results can be accepted and/or trusted. The objective of our study was to identify and characterise the procedural and practical constraints as well as to assess their potential effects on autopsy outcomes in Ghana. We interviewed 10 Ghanaian pathologists and collected and evaluated procedural manuals and operational procedures for the conduct of autopsies. A characterisation of the operational constraints and the Delphi analysis of their potential influence on the quality of mortality data led to a quantification of the validity threats as moderate (average expert panel score = 1) in the generality of the autopsy operations in Ghana. On the basis of the impressions of the expert panel, it was concluded that mortality data generated from autopsies in urban settings in Ghana were of sufficiently high quality to guarantee valid use in health analysis

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm